Phototherapeutic wave guide apparatus

ABSTRACT

Methods and apparatus are disclosed for forming annular lesions in tissue. The methods include introduction of an optical apparatus proximate to a tissue site, via, for example, a catheter. The optical apparatus includes a pattern-forming optical wave guide in communication with a light transmitting optical fiber. Energy is transmitted through the optical fiber, such that radiation is propagated through the optical fiber and the wave guide projects an annular light pattern, e.g., a circle or a halo.

FIELD OF THE INVENTION

[0001] The technical field of this invention is phototherapy and, inparticular, methods and devices which employ optical fibers and flexiblelight waveguides to deliver radiation to a targeted site.

BACKGROUND OF THE INVENTION

[0002] Destruction of cellular tissues in situ has been used in thetreatment of diseases and medical conditions alone or as an adjunct tosurgical removal procedures. These methods are often less traumatic thansurgical procedures and may be the only alternative where surgicalprocedures are unfeasible. Phototherapeutic treatment devices, e.g.,lasers, have the advantage of using intense light energy which israpidly attenuated to a non-destructive level outside of the targetregion. However, blood and/or other body fluids greatly diminish theeffectiveness of several of these light energy sources as the radiationpasses from an energy source, e.g., a laser source, through the bodyfluid to a treatment site. For example, the energy can be scattered orbe absorbed by blood and other body fluids between the energy source andthe tissue treatment site.

[0003] A common medical application of lasers is in the irradiation oftissue, both internal and external. For external treatment, the laserenergy can be applied directly. However, where a procedure requiresirradiation of internal tissues that are not readily accessible toexternal energy sources, the use of catheter-type devices to delivercoherent radiation to the treatment site is common. Typical applicationsrequiring use of laser catheters are found in the treatment of variousanatomical structures and conditions within the cardiovascular system.

[0004] Microwave, radio frequency, and acoustical (ultrasound) devicesas well tissue destructive substances have also been used to destroymalignant, benign and other types of aberrant cells in tissues from awide variety of anatomical sites and organs. Tissues sought to betreated include isolated carcinoma masses and, more specifically, organssuch as the prostate, bronchial passage ways, passage ways to thebladder, passage ways to the urethra, and various passage ways into thethoracic area, e.g., the heart.

[0005] Devices useful for the treatment of such disease states orconditions typically include a catheter or an cannula which can be usedto carry an energy source or waveguide through a lumen to the zone oftreatment. The energy is then emitted from the catheter into thesurrounding tissue thereby destroying the diseased tissue, and sometimessurrounding tissue.

[0006] Catheters have been utilized in the medical industry for manyyears. One of the greatest challenges in using a catheter is controllingthe position and placement of the distal portion of the catheter from aremote location outside of the subject's body. Some catheters havefeatures designed to aid in steering the catheter and overcoming thischallenge. However, several significant problems are still encounteredwith catheters.

[0007] Careful and precise control over the catheter is required duringcritical procedures which ablate tissue within the heart. Suchprocedures are termed “electrophysiological” therapy and are becomingwidespread for treatment of cardiac rhythm disturbances. During theseprocedures, an operator guides a catheter through a main artery or veininto the interior of the heart which is to be treated. The operatormanipulates a mechanism to cause an electrode which is carried on thedistal tip of the catheter into direct contact with the tissue area tobe treated. Energy is applied from the electrode into the tissue andthrough an indifferent electrode (in a uni-polar electrode system) or toan adjacent electrode (in a bi-polar electrode system) to ablate thetissue and form a lesion. The irradiation of tissue must be accomplishedwith great precision as the danger of also damaging other adjacenttissue is always present, especially when the process occurs remotely atthe distal end of a relatively long catheter.

[0008] One partial solution to this problem has been to “map” the areato be treated prior to a procedure. Cardiac mapping can be used prior toablation to locate aberrant conductive pathways within the heart. Theaberrant conductive pathways are called arrhythmias. Mapping of theheart identifies regions along these pathways, termed “foci”, which arethen ablated to treat the arrhythmias.

[0009] During laser ablation procedures, a catheter serves to deliver afiber optic wave guide to the target region. Radiation transmittedthrough the optical fiber essentially vaporizes the targeted tissue toachieve the desired therapeutic goals of the procedure. Completedestruction of target tissue, with the exception of certain narrow andspecific cardiac treatments, is generally limited to cardiologicalapplications, e.g., removal of a blockage. In electrophysiologicaltreatments, total destruction of target tissue (ablation) is notnecessary, but controlled denaturation of tissue to affect itselectrophysiological properties is required.

[0010] Within the heart, variations in cardiac tissue characteristics,perhaps as the result of scarring from previous cardiac trauma, canpresent vastly different tissue that react differently to the laserenergy source. For example, absorption characteristics of normal tissuecan be much different from tissue that is heavily scarred. In addition,the trabecular nature of the endocardium increases the difficultybecause the laser radiation must reach a highly contoured or foldedtarget tissue surface. As a result, temperatures of the tissue surfacewhere the laser energy is incident can be much higher for some tissuethan for others. In the treatment of cardiac tissue, the dynamic stateof the heart tissue further complicates the situation in that the heartis constantly moving during treatment. Thus, incorporation of fixationmeans to maintain the position of the distal end of the laser catheterwith respect to the target tissue site is often required.

[0011] There are drawbacks with many of the currently availablecatheters and treatments. Oftentimes it is difficult, if not impossible,to maneuver the instrument into small passage ways, such as a ventricle,without damaging the surrounding tissue. Most therapeutic treatmentsrequire that the apparatus is in contact with the tissue and with bloodand/or other body fluids. Additionally, focusing the ablative energyonto the tissue site to be treated can be problematic, especially whenvital organs surround the diseased tissue. Therefore, it would bedesirable to focus ablative energy onto a specific treatment areawherein surrounding tissue is not degraded, the energy source is not indirect contact with the tissue and blood and body fluids are notcoagulated or destroyed.

SUMMARY OF THE INVENTION

[0012] The present invention circumvents the problems described above bydelivering energy, e.g., laser light or other ablative energy, in anannular pattern without requiring direct contact with an energy source,e.g. a laser (via fiber), with the targeted tissue. This indirectcontact with the targeted tissue provides an advantage that damage tosurrounding tissues is minimized or eliminated. More specifically, incardiac therapy, another advantage is that an annular conduction blockis created about the pulmonary vein orifice, thereby eliminatingaberrant wave conduction.

[0013] In one embodiment, the present invention includes an apparatusfor inducing phototherapeutic processes in tissue which can includeablation and/or coagulation of the tissue. Typically the opticalapparatus is contained within a catheter including a flexible elongatemember having a proximal end, a distal end and a longitudinal firstlumen extending therebetween. The distal end of the flexible elongatemember is open or includes a transparent cap, a centering balloon, or acentering coil. The optical apparatus of the invention can be slidablyextended within the first lumen for projecting light through or from thedistal end of the flexible member. Alternatively, the optical fiber andother light projecting elements can be fixed in place with the catheter.

[0014] The optical apparatus of the invention includes an optical waveguide for projecting an annular pattern of light and a lighttransmitting optical fiber. Radiation, e.g., infrared, visible orultraviolet light is propagated through the optical fiber which is incommunication with the pattern-forming wave guide. The wave guide/lensis configured to project an annular light pattern such that an annularlesion is formed in tissue. In one embodiment, the annular light patternexpands over distance and is in the form of a ring or a halo. Theoptical apparatus includes a graded intensity lens (GRIN) or standardrefractive optics in addition to the optical wave guide to project theannular light pattern.

[0015] In certain embodiments, the optical apparatus of the invention isslidably positioned within the lumen of a catheter proximate to a tissuesite. The catheter can include a balloon member fixedly attached to thecatheter. Injection of a solution or gas expands the balloon, therebyforcing blood and/or other body fluids from the tissue site. Positioningthe optical apparatus permits control over the size of the forwardlyprojected annular ring to be dynamically changed to accommodate variedpulmonary vein diameters.

[0016] The present invention also pertains to methods for forming anannular lesion in a tissue by phototherapeutic processes in tissue whichcan include ablation and/or coagulation of the tissue. The methodsinclude introduction of an optical apparatus proximate to a tissue sitevia, for example, a catheter. The optical apparatus includes apattern-forming optical wave guide that is in communication with a lighttransmitting optical fiber. Energy is transmitted through the opticalfiber, such that radiation propagated through the optical fiber and waveguide projects an annular light pattern, e.g., a circle or a halo. Bythese methods, an annular lesion can be formed in a targeted tissue. Incertain embodiments, the tissue forms a lumen, e.g., vascular, atrial,ventricular, aterial, brachial, or uretral lumen. Preferably the methodsinclude projecting an annular light pattern through a graded intensitylens that is adjacent to the optical wave guide. This additional stepforwardly projects the light pattern.

[0017] The present invention further pertains to methods for formingannular lesions in cardiac tissue, e.g., trabecular tissue, byphototherapeutic processes which can include ablation and/or coagulationof the tissue. The methods include introduction of an optical apparatusproximate to the cardiac tissue via, for example, a catheter. Theoptical apparatus includes a pattern-forming optical wave guide incommunication with a light transmitting optical fiber. Energy istransmitted through the optical fiber, such that radiation is propagatedthrough the optical fiber, the wave guide and GRIN lens to forwardlyproject an annular light pattern, e.g., a circle or a halo. In apreferred embodiment, a balloon is inflated against the tissue, therebyforcing blood and/or body fluids away from the tissue targeted fortreatment. Light energy is then passed through the optical apparatusonto the targeted tissue such that an annular image is projected ontothe site which causes ablation, coagulation or photochemical processesto occur.

[0018] The present invention also pertains to methods for treating orpreventing atrial arrhythmias by phototherapeutic processes in atrialtissue. These processes can include ablation and/or coagulation of thetissue. The methods include introducing an optical apparatus proximateto atrial tissue via, for example, a catheter. The optical apparatusincludes an optical wave guide in communication with a lighttransmitting optical fiber. Energy is transmitted through the opticalfiber, such that radiation is propagated through the optical fiber andthe wave guide projects an annular light pattern. The annular lightpattern forms an annular lesion in the atrial tissue, thereby treatingor preventing atrial arrhythmias.

[0019] The methods of the invention can be performed therapeutically orprophylactically. In one embodiment, the treatment method is performedon the atrial wall around the atrial/pulmonary vein juncture or aroundthe pulmonary vein, or within the pulmonary vein. A circular orring-like section within the pulmonary vein is created by the method ofthe invention. Formation of one or more circular lesions about theoutside or inside diameter of the vein, impedes the conduction ofirregular electrical waves to the atrium.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Other objects, advantages and features of the present inventionwill be readily appreciated as the same becomes better understood byreference to the following detailed description when considered inconnection with the accompanying drawings, in which like referencenumerals designate like parts throughout the figures thereof andwherein:

[0021]FIG. 1 is a schematic view of an optical apparatus of theinvention which projects an annular beam of light from a modified waveguide;

[0022]FIG. 2 is a cross sectional view of a modified wave guide of theinvention;

[0023]FIG. 3 is another cross sectional view of a modified wave guide ofthe invention;

[0024]FIG. 4 is still another cross sectional view of a modified waveguide encompassed by the invention;

[0025]FIG. 5 is yet another cross sectional view of a modified waveguide useful with the present invention;

[0026]FIG. 6 is still yet another cross sectional view of a modifiedwave guide useful in the present invention;

[0027]FIG. 7 is another cross sectional view of a modified wave guide ofthe invention;

[0028]FIG. 8 is an optical apparatus of the invention bonded by a meltformed polymeric material;

[0029]FIG. 9 is a cross-sectional view of the distal end portion of anembodiment of the invention having an optical apparatus and a ballooncontained within a tubular body lumen in an uninflated state;

[0030]FIG. 10 is a cross-sectional view of the device of FIG. 9following inflation of the balloon;

[0031]FIG. 11 is a cross-sectional view of another intraluminal deviceof the invention with the balloon in an uninflated stated and stowedwithin the lumen of the flexible elongate member;

[0032]FIG. 12 is a cross-sectional view of a catheter device of FIG. 11after a gas or solution has been added through the lumen of the flexibleelongate member;

[0033]FIG. 13 is a cross-sectional view of a preferred device of theinvention including an inflated balloon attached to a flexible elongatemember having an optical apparatus contained therein;

[0034]FIG. 13A is an expanded cross-sectional view of the opticalapparatus of FIG. 13;

[0035]FIG. 14 is a depiction of annular lesions located at theatrium/pulmonary vein interface;

[0036]FIG. 15 is a schematic block diagram of a laser tissue treatmentsystem according to the present invention; and

[0037]FIG. 16 is a detailed schematic diagram of a reflectance monitorfor use in the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0038] The features and other details of the invention will now be moreparticularly described and pointed out in the claims. It will beunderstood that the particular embodiments of the invention are shown byway of illustration and not as limitations of the invention. Theprinciple features of this invention can be employed in variousembodiments without departing from the scope of the invention.

[0039] The present invention is based, at least in part, on a discoverythat the present invention can be used for inducing hyperthermia,coagulation or phototherapeutic processes in tissue, e.g., ablation,degradation, or destruction of tissue, at a specified site in tissuewithout harming the surrounding tissue. The results are surprising andunexpected since the efficiency and efficacy coherent light is generallydiminished by light scatter, formation of “hot spots” due to inefficientlight scatter, by the limitation that the light emitted from an opticalfiber continues in a straight path, and/or from interaction(s) withblood and/or body fluids which surround a tissue site to be treated.

[0040] Prior to this invention, the energy emitter, e.g., a lasersource, ultraviolet light, microwave radiation, radio-frequency, etc.,has generally been required to be in contact with the tissue to effect atherapeutic or prophylactic treatment. In contrast to known apparatusesand methods, the present invention does not require direct contactbetween the energy source, e.g., a laser source, and the tissue site tobe treated. Moreover, in certain embodiments the methods and apparatusof the invention circumvent the drawbacks of having blood or body fluidcoagulate, degrade or be destroyed in the treatment area proximate tothe targeted tissue due to interactions with the applied energy.

[0041] In one embodiment, the present invention is drawn to an apparatusfor inducing phototherapeutic processes in tissue. These processes caninclude ablation and/or coagulation. Typically the optical apparatus iscontained within a catheter including a flexible elongate member havinga proximal end, a distal end and a longitudinal first lumen extendingtherebetween. The distal end or a portion of the distal end of theflexible elongate member is open, transparent, or includes a transparentcap. The optical apparatus of the invention can be slidably extendedwithin the first lumen for projecting light through or from a distal endportion of the flexible member.

[0042] The optical apparatus of the invention includes a pattern-formingoptical wave guide for annularly projecting a pattern of light and alight transmitting optical fiber. Radiation, is propagated through theoptical fiber which is in communication with the wave guide. The waveguide is configured to forwardly project an annular light pattern suchthat an annular lesion is formed in tissue. Typically, the annular lightpattern is projected at an angle between about 20 and 45 degrees fromthe center plane of the optical fiber. In one embodiment, the annularlight pattern expands over distance and is in the form of a ring or ahalo. Preferably, the optical apparatus further includes a gradedintensity lens (GRIN) adjacent to the optical wave guide for attenuatingany aberrations in the light pattern.

[0043] The present invention provides the advantage that the annularlight pattern is forwardly projected. The invention further providesthat the angle of projection can be attenuated by a GRIN lens and/or bythe dimensions of a balloon, described infra, located proximate to theoptical apparatus. In contrast, current apparatus' project lightperpendicular to the central axis of the energy conduit, e.g., theoptical fiber/wave guide. These apparatus, therefore, do not provide theability to focus an annular ring about a preselected site in front ofthe light emitting apparatus as provided by the present invention.Consequently, the present invention provides the ability to focus energyonto a specific site, unlike cryogenic or sonic techniques which treat asite along with tissue which surrounds the site due to energydissipation about the treatment site.

[0044] The term “phototherapeutic” is intended to include photoablative,photochemical and photothermal processes which are therapeutic and/orprophylactic in a subject.

[0045] The terms “ablate” or “ablation” or “photothermal” are wellrecognized in the art and are intended to include thermal coagulationand/or removal of tissues which are necrotic, damaged, or are aberrantin nature. Ablation also includes the desiccation of tissue by theapplication of heat. For example, an ablating energy, such as thosedescribed above, would be one that would cause the tissue to reach atemperature of between about 60-90° C. Ablation increases thephysiological temperature of a tissue by energetic stimulation to atemperature which degrades or eradicates tissue, thereby removingdiseased tissue from a localized area. Ablation can be used as atherapeutic treatment, where diseased or otherwise unwanted tissue orcells exist, or as a preventative treatment to inhibit exigentphysiological aberrations, e.g., arrhythmias e.g., fibrillations orflutters, growth of undesirable tissue or cells in a specific region ofan organ or viscera. In order to obtain destruction of tissueexclusively by thermal effects, it is necessary for the energy to beable to reach a threshold of destruction referred to as the “thermaldose”. This threshold is a function of temperature reached and of theduration of the application. Therefore, ablation, to some degree, isbased on the rise of the local temperature of tissue.

[0046] The term “coagulation” is well recognized in the art and isintended to mean the action whereby cells and/or body fluids within atreated tissue site are caused to become necrosed, thickened and/or losethe ability to conduct electrical activity, thereby resulting in acoherent mass by the methods of the invention. The method and apparatusof the invention permit selective, coagulation of a targeted tissue areaand not blood or other body fluids which are found external, e.g.,surrounding, to the target site.

[0047] The term “body fluids” is intended to encompass those naturallyoccurring physiological components produced by a subject to maintainstasis. These fluids typically include physiological components such asplasma, growth factors, platelets, lymphocytes, granulocytes, etc.

[0048] The term “photochemical” is well recognized in the art andincludes various energetic processes, including chemical reactionsinitiated by photons generated by an energy source. Typicallyphotochemical processes are associated with laser, ultra-violet light,visible light or infrared light. Photochemical processes include thegeneration of radicals by photons colliding with tissue. The radicalspecies are generated within cell tissue, often times causing oxidationof the cell contents; degradation or eradication occurs after theradical species are generated. In the method of the invention,photochemical reactions are selective for the targeted tissue area andnot blood or other body fluids which are found external to the targetedtreatment site.

[0049] Photochemical processes cause injury to cells and tissue eitherby mechanical lysis or by the generation of by-products such as freeradicals, e.g., such as HO₂., OH⁻., HO. and H₂O., which damage celland/or tissue membrane. These reactive by-products can interact with thelocalized surrounding tissue area such that the tissue is cleansed ofunwanted material. Photochemical processes can involve oxidation orradical polymerization of, for example, cell walls, extracellular matrixcomponents, cell nuclei, etc. Such photochemical processes can beinduced by infrared, visible and ultraviolet light energy.

[0050] The terms “into” and “onto” are used interchangeably and areintended to include treatment of tissue by focusing energy, e.g.,ablative, coagulative, or photothermal, toward the afflicted area. Insome instances the energy penetrates the tissue and in other instancesthe energy only superficially treats the surface of the tissue. Anordinary skilled artisan would understand what depths of penetration arerequired and those parameters which are dependent upon the application,tissue type, area to be treated and severity of condition. Accordingly,the amount of energy used to treat the afflicted area would beattenuated based upon the disease or condition being treated.

[0051] “Interstitial cavity,” as the term is used herein, encompassesinterstices in a tissue or structure of a natural body structure, spacesand gaps existing between layers of tissue or existing within organs,and can include interstices within the interior of the ureter, bladder,intestines, stomach, esophagus, trachea, lung, blood vessel or otherorgan or body cavity, and will be further understood to include anysurgically created interstice that defines an interior cavity surroundedby tissue.

[0052] The term “wave guide” is well recognized in the art and isintended to include those devices that constrain or guide thepropagation of electromagnetic radiation along a path defined by thephysical construction of the guide. Several wave guides are ofimportance, including hollow-pipe waveguides and dielectric waveguides.Hollow-pipe guides are used primarily in the microwave region of thespectrum, dielectric guides primarily in the optical region. An infinitenumber of guide shapes are possible, including circular triangular,rectangular, or square and combinations thereof. Consequently, there arean infinite number of projections possible based upon the shape of thewave guide, e.g., annular, e.g., a ring or halo, and the outlines of atriangle, rectangle, or square and combinations thereof.

[0053] In preferred embodiments, the electromagnetic radiation, e.g.,coherent light, is emitted from the wave guide such that the projectedenergy expands uniformly over a distance. For example, annularprojection of laser light from a circular wave guide forms an expandingcone. The angle of the cone of light is dependent upon the angle ofreflection within the wave guide, the concavity of inner walls withinthe wave guide and the distance to an object to which it is projected.For example, as shown in FIG. 1, optical apparatus 10 includes andoptical fiber 12 in communication with an optical wave guide 14 having aconcave interior. Modified wave guide 14 projects an annular beam oflight through a GRIN lens 26, e.g., a halo, 16 from distal portion 18 ofwave guide 14 over a distance, d,. Typically, the angle of projectionfrom the central axis of the optical fiber 12 or wave guide 14 isbetween about 20 and 45 degrees.

[0054] As shown in FIG. 1, the projection of a beam of light from waveguide 14 expands over distance d₁, thereby forming an annulus, anoutline of a shape formed from light passing through a modified waveguide 14 and GRIN lens 26, having a diameter which is generally largerthan the diameter of distal portion 18 of wave guide 14. The diameter ofthe annular beam of light 16 is dependent upon the distance d₁ from thepoint of projection to point of capture by a surface, e.g., a tissuesite, e.g., an interstitial cavity or lumen. The width, w₂, of theannulus is dependent upon the width w₁ of distal end 18, distance d₁,distance d₂, and angles α₁ and α₂. Width w₂ is typically between about0.5 mm to about 5 mm, preferably between about 1 mm to about 4 mm, mostpreferably between about 2 mm and about 3 mm. Varying angles α₁ and α₂and distance d₂ maximizes or minimizes angle α₃ about the central axisas depicted in FIG. 1. Typically, angle α₃ of projected annular light isbetween about 15 and about 45 degrees, preferably between about 16 andabout 30 degrees, most preferably between about 17 and about 25 degrees.

[0055] As shown in FIGS. 1, 2 and 3, the width, w₁, of distal portion 18can be minimized or maximized depending upon where the modified portion,e.g., the concave portion, within wave guide 14 terminates. Typicallywidths, w₁ as shown in FIGS. 2 and 3, are between about 0.05 mm andabout 1.0 mm, inclusive, more preferably between about 0.1 mm and about0.5 mm, most preferably between about 0.1 mm and about 0.2 mm,inclusive. The distal portion 18, therefore, can be a rim which hassubstantially no appreciable width, w₁, e.g., a point where the exteriorwall 20 of wave guide 14 and interior wall 22 intersect (FIG. 3). Ingeneral, the diameter of wave guide 14 is between about 0.2 mm to about1.0 mm, inclusive, more preferably between about 0.3 mm to about 0.8 mm,inclusive, and most preferably between about 0.4 mm to about 0.7 mm,inclusive.

[0056]FIGS. 4 and 5 depict alternative embodiments of modified waveguide 14 where the interior walls 22 of the tapered concave surface meetat position 24 within wave guide 14. In certain embodiments position 24,where the tapered interior walls meet, is centrally located, in otherembodiments position 24 can be off axis. In one aspect, position 24,where tapered interior walls 22 meet, is planar and can have a width,w₃, which is between about 0.05 mm and about 0.5 mm, inclusive,preferably between about 0.1 mm and about 0.3 mm, inclusive, and mostpreferably between about 0.2 mm and about 0.3 mm, inclusive. In anotheraspect, position 24 can be cup shaped. As shown in FIG. 4, distalportion 18 is a rim formed by external wall 20 and interior wall 22. Asshown in FIG. 5, distal portion 18 has width, w₁, as described above.

[0057]FIGS. 6 and 7 depict still other alternative embodiments of waveguide 14 where the interior walls 22 of the tapered concave surface meetat position 24 within wave guide 14. In certain embodiments position 24,where the tapered interior walls meet, is centrally located, in otherembodiments position 24 can be off axis. In one aspect, interior walls22 are asymptotic. As shown in FIG. 6, distal portion 18 is a rim formedby external wall 20 and interior wall 22. As shown in FIG. 7, distalportion 18 has width, w₁, as described above.

[0058] Wave guides, as described in above and in FIGS. 1-7 can be madefrom materials known in the art such as quartz, fused silica or polymerssuch as acrylics. Suitable examples of acrylics include acrylates,polyacrylic acid (PAA) and methacrylates, polymethacrylic acid (PMA).Representative examples of polyacrylic esters include polymethylacrylate(PMA), polyethylacrylate and polypropylacrylate. Representative examplesof polymethacrylic esters include polymethylmethacrylate (PMMA),polyethylmethacrylate and polypropylmethacrylate.

[0059] Internal shaping of the wave guide can be accomplished byremoving a portion of material from a unitary body, e.g., a cylinder orrod. Methods known in the art can be utilized to modify wave guides tohave tapered inner walls, e.g., by grinding, milling, ablating, etc.Preferably, a hollow polymeric cylinder, e.g., a tube, is heated so thatthe proximal end collapses and fuses together, forming an integralproximal portion which tapers to the distal end of the wave guide. In apreferred embodiment, the wave guide is flexible.

[0060] Wave guide 14 is in communication, e.g., connected, with opticalfiber 12 by methods known in the art. These methods include for example,glueing, or fusing with a torch or carbon dioxide laser. In oneembodiment shown in FIG. 8, wave guide 14, optical fiber 12 and,optionally, a gradient index lens (GRIN) 26 are in communication and areheld in position by welding with a polymeric material 28, such asTEFLON®, e.g., by melting the polymeric material about the opticalapparatus 10 and, optionally, GRIN 26.

[0061] The terms “gradient index lens” or “graded index lens” (GRIN) arewell recognized in the art and are intended to mean those lenses whichhave a refractive index distribution, which takes place in a parabolicmanner so that the refractive index is greatest at the central axis ofthe rod and so that the refractive index is progressively reduced fromthe central axis toward the periphery of the rod. As a result, thepenetrating light is caused to move inside the rod in a zigzag manner.The shape of the GRIN lens can be cylindrical, oval, round, or convex.

[0062] The term “flexible elongate member” is well recognized in the artand is intended to refer to a hollow tube having at least one lumen. Ingeneral, a flexible elongate member is often termed a “catheter”, a termwhich is well known in the art. The flexible elongate member hasproximal and distal ends with at least one longitudinal lumen extendingtherebetween. The distal end can be open or closed as is known in theart. In one embodiment, the distal end of the flexible elongate memberis open, thereby allowing an optical apparatus of the invention toprotrude beyond the elongate member, e.g., into a catheter end, e.g.,into a balloon member. In another embodiment, the distal portion of theelongate member is closed, thereby preventing an optical apparatus frompassing beyond the distal end of the elongate member.

[0063] Flexible elongate members, e.g., tubular catheters, can be formedfrom biocompatible materials known in the art such as cellulosic ethers,cellulosic esters, fluorinated polyethylene, phenolics,poly-4-methylpentene, polyacrylonitrile, polyamides, polyamideimides,polyacrylates, polymethacrylates, polybenzoxazole, polycarbonates,polycyanoarylethers, polyesters, polyestercarbonates, polyethers (PEBAX,polyether block amide), polyetherketones, polyetherimide,polyetheretherketones, polyethersulfones, polyethylene, polypropylene,polyfluoroolefins, polyimides, polyolefins, polyoxadizoles,polyphenylene oxides, polyphenylene sulfides, polysulfones,polytetrafluoroethylene, polythioethers, polytraizoles, polyurethanes,polyvinyls, polyvinylidene fluoride, silicones, urea-formaldehydepolymers, or copolymers or physical blends thereof.

[0064] Preferably, the materials used to construct the flexible elongatemember or the catheter end portion can be “transparent” materials, suchas fluoropolymers. Suitable transparent materials include polyethylene,nylon, polyurethanes and silicone containing polymers, e.g., silastic.Suitable fluoropolymers include, for example, fluorinated ethylenepropylene (FEP), perfluoroalkoxy resin (PFA), polytetrafluoroethylene(PTFE), and ethylene-tetrafluoroethylene (ETFE). Typically the diameterof the flexible elongate member is between about 0.050 inches and about0.104 inches, preferably between about 0.060 inches and about 0.078inches. The diameter of at least one inner lumen of the flexibleelongate member is between about 0.030 inches and about 0.060 inches,preferably between about 0.040 inches and about 0.050 inches. The lengthof the flexible elongate member varies with the intended application andin generally between about 60 cm and about 145 cm in length. For cardiacapplications the flexible elongate member is between about 80 cm, andabout 125 cm long, for bronchial applications the flexible elongatemember is 125 cm long.

[0065] The term “catheter” as used herein is intended to encompass anyhollow instrument capable of penetrating body tissue or interstitialcavities and providing a conduit for selectively injecting a solution orgas, including without limitation, venous and arterial conduits ofvarious sizes and shapes, bronchioscopes, endoscopes, cystoscopes,culpascopes, colonscopes, trocars, laparoscopes and the like. Cathetersof the present invention can be constructed with biocompatible materialsknown to those skilled in the art such as those listed supra, e.g.,silastic, polyethylene, Teflon, polyurethanes, etc.

[0066] Typically, the optical apparatus of the invention is positionedproximate to the tissue targeted for treatment within a catheter. Thecatheter has been positioned proximate to the targeted tissue site andprovides that the optical apparatus can be slidably positioned proximateto the tissue, thereby avoiding direct contact with the tissue and/orbody fluids. In a preferred embodiment, a balloon is inflated againstthe tissue, thereby forcing blood and/or body fluids away from thetissue targeted for treatment. Light energy is then passed through theoptical apparatus, a GRIN lens and balloon onto the targeted tissue suchthat an annular image is projected onto the site which causes ablation,coagulation and/or phototherapeutic processes to occur within thetissue.

[0067] The term “biocompatible” is well recognized in the art and asused herein, means exhibition of essentially no cytotoxicity while incontact with body fluids or tissues. “Biocompatibility” also includesessentially no interactions with recognition proteins, e.g., naturallyoccurring antibodies, cell proteins, cells and other components ofbiological systems.

[0068] The term “transparent” is well recognized in the art and isintended to include those materials which allow diffusion of energythrough, for example, the flexible elongate member, the tip, cap and/ora catheter end. Preferred energy transparent materials do notsignificantly impede (e.g., result in losses over 20 percent of energytransmitted) the energy being transferred from a optical apparatus tothe targeted tissue or cell site. Suitable transparent materials includefluoropolymers, for example, fluorinated ethylene propylene (FEP),perfluoroalkoxy resin (PFA), polytetrafluoroethylene (PTFE), andethylenetetrafluoroethylene (ETFE).

[0069] The term “fixedly attached” is intended to include those methodsknown in the art to attach a catheter end portion, cap, or balloon tothe distal portion of a flexible elongate member. Various means areknown to those skilled in the art for fixedly attaching individualmembers of the present apparatus to each other. Such methods includethermal welding or glueing the two materials together to form a uniformseam which will withstand stresses placed upon the integral seam. Forexample, the catheter end portion or a tip is welded, e.g., thermal,photochemical, sonically, e.g., ultrasound, or glued, at the proximalmost portion of the catheter end or tip to the distal end of theflexible elongate member. In another embodiment, the proximal end of thecatheter end is affixed to the distal end of the elongate member whichis itself a sealed, e.g., having a tip or a cap.

[0070] The terms “tip” or “cap” are well recognized in the art and areintended to include those devices which are used to seal the end of aluminal body. In one embodiment, the cap is non-metallic. In certainembodiments, the cap is non-porous. In a preferred embodiment, the capis non-metallic and non-porous, e.g., a polymeric material.

[0071] The term “catheter end portion” is intended to include a separateattachable, and in certain embodiments, detachable, catheter-likeportion which is located proximate to the distal end of a catheter. Thecatheter end portion can be fixedly attached or integrally locked intoplace on the distal end of a catheter by methods known in the art, e.g.,glueing, melting, ultrasonic welding, “snap on” fittings, male-femalefittings, etc. Preferably the catheter end portion is energytransparent. An example of a catheter end portion is a silicone balloonanchor.

[0072] The term “control handle” is well recognized in the art and isintended to include various means to manipulate the apparatus of theinvention, including at least the flexible elongate member, guidewiresif present, and the optical apparatus. Various control handles usefulwith the present invention are commercially available, such as thosemanufactured by Cordis Webster, Inc., 4750 Littlejohn St., Baldwin Park,Calif., 91706. When used, the control handle applies tension, e.g.,stress, to the proximate end of a guidewire, thereby causing the distalend of the guidewire to bend, distort or deform. As a consequence ofthis action, the flexible elongate member to which the guidewire isattached, also bends, distorts or deforms in the same plane as theguidewire.

[0073] The phrase “light transmitting optical fiber” is intended toinclude those fibers, glass, quartz, or polymeric, which conduct lightenergy in the form of ultraviolet light, infrared radiation, or coherentlight, e.g., laser light.

[0074] An exemplary manufacturing process suitable for joining the waveguide to a glass-clad or polymer-clad optical fiber having an outerdiameter of about 50 to 1,000 micrometers can begin by stripping off abuffer from the end of the fiber, e.g., exposing about 2 or 3millimeters of the inner fiber core and its cladding. (It is notnecessary to strip the cladding away from the core.) Prior to stripping,the fiber end face preferably should be prepared and polished as isknown in the art to minimize boundary or interface losses.

[0075] In one embodiment, a transparent tubular structure will form ahousing and attaching means for the wave guide and prepared fiber end.The fiber and wave guide are positioned such that they located so thatthe distal end of the stripped fiber and the proximal end of the waveguide are in communication. The tubular structure can be slid over thetwo components, thereby fixing the respective ends to each other.Preferably, a GRIN lens is placed in communication with the distal endof the wave guide and contained within the tubular structure. In onepreferred embodiment, the housing is a Teflon® FEP tubing available, forexample, from Zeus Industries (Raritan, N.J.). The transmission spectrumof Teflon® FEP shows that this material is well suited for a scattererencasing material across a spectrum of light ranging from the infraredto ultraviolet.

[0076] Preferred energy sources include laser light, in the rangebetween about 200 nanometers and 10.5 micrometers. In particular,wavelengths that correspond to water absorption peaks are oftenpreferred. Such wavelengths include those between about 900 and about950 nm, inclusive, preferably 910 and about 920 nm, most preferably, 915nm. Suitable lasers include excimer lasers, gas lasers, solid statelasers and laser diodes. A particularly preferred AlGaAs diode array,manufactured by Optopower, Tucson, Ariz., produces a wavelength of 915nm. A preferred energy is coherent light, e.g., laser light, in therange between about 200 nm to about 2.4 μm, preferably between about 400to about 3,000 nm, more preferably between about 805 and 1060 nm.Typically the conductor emits between about 2 to about 10 watts/cm oflength, preferably between about 4 to about 6 watts/cm, most preferablyabout 4 watts/cm.

[0077] In one embodiment, the optical apparatus can extend beyond thedistal end of the flexible elongate member. In certain embodiments, theoptical apparatus slidably extends into a lumen created by a balloonfilled with a suitable solution or gas. Alternatively, the opticalapparatus can be slidably located or fixed within a transparent flexibleelongate member about which surrounds an inflated balloon. In thisembodiment, the light is projected annularly through the transparentflexible elongate member, through an inflation solution and into theinflated balloon and onto the targeted treatment site.

[0078] The light transmitting optical fiber transmits the energy from anenergy source which is in communication with the optical fiber. Suitableenergy sources are known in the art and produce the above-mentionedtypes of energy. Preferred laser sources include diode lasers. Theoptical fiber is positioned within lumen formed by a flexible elongatemember (described supra). The optical fiber can be slidably controlledwithin the lumen such that positioning of the optical fiber within theflexible elongate member is readily achieved. Preferably, the opticalfiber is positioned proximate to the expanded balloon member.

[0079] The balloon, e.g., a biocompatible balloon, is affixed to thecatheter body member near the distal end and is in fluid communicationwith at least one of inflation port. Upon injection of solution, theexpandable balloon inflates forming a lumen or “reservoir” between thecatheter body and the outerwall of the balloon. It should be understoodthat the term “balloon” encompasses deformable hollow shapes which canbe inflated into various configurations including balloon, circular,tear drop, etc., shapes dependent upon the requirements of the bodycavity.

[0080] The terms “treat”, “treatment” or “treating” are intended toinclude both prophylactic and/or therapeutic applications. The methodsof the invention can be used to protect a subject from damage or injurycaused by a disease, physical aberration, electrical aberration, or canbe used therapeutically or prophylactically treat the subject after theonset of the disease or condition.

[0081] The term “subject” is intended to include mammals susceptible todiseases, including one or more disease related symptoms. Examples ofsuch subjects include humans, dogs, cats, pigs, cows, horses, rats andmice.

[0082] The term “tissue” is well recognized in the art and is intendedto include extracorporeal materials, such as organs, e.g., mesentery,liver, kidney, heart, lung, brain, tendon, muscle etc.

[0083] The term “disease” is associated with an increase of a pathogenwithin a subject such that the subject often experiences physiologicalsymptoms which include, but are not limited to, release of toxins,gastritis, inflammation, coma, water retention, weight gain or loss,ischemia and immunodeficiency. The effects often associated with suchsymptoms include, but are not limited to fever, nausea, diarrhea,weakness, headache and even death. Examples of diseases which can betreated by the present invention include undesirable cell proliferation,bacterial infection, cancer, e.g., bladder, urethral, mammarian, ovarianand lung cancer, or, ischemia, and benign prostatic hypertrophy orhyperplasia (BPH).

[0084] The language “undesirable cell proliferation” is intended toinclude abnormal growth of cells which can be detrimental to a subject'sphysiological well being. Effects of undesirable cell proliferation caninclude the release of toxins into the subject, fever, gastritis,inflammation, nausea, weakness, coma, headache, water retention, weightgain or loss, immunodeficiency, death, etc. The undesired cells whichproliferate can include cells which are either benign or malignant.Examples of undesirable cell proliferation include bacterial cellproliferation and aberrant cell division and/or proliferation of foreigncells, such as in cancer cells.

[0085] The terms “aberrant cell” or “aberrant tissues” as used herein,are well recognized in the art and are intended to include aberrant celldivision and/or proliferation where cells are generated in excess ofwhat is considered typical in physiologically similar environment, suchas in cancers.

[0086] The language “control of undesirable cell proliferation” or“controlling undesirable cell proliferation” is intended to includechanges in growth or replication of undesired cells or eradication ofundesired cells, such as bacteria, cancer, or those cells associatedwith abnormal physiological activity. The language includes preventingsurvival or inhibiting continued growth and replication of an undesiredcell. In one preferred embodiment, the control of the undesired cell issuch that an undesired cell is eradicated. In another preferredembodiment, the control is selective such that a particular targetedundesired cell is controlled while other cells, which are notdetrimental to the mammal, are allowed to remain substantiallyuncontrolled or substantially unaffected, e.g., lymphocytes, red bloodcells, white blood cells, platelets, growth factors, etc.

[0087] The term “cancer” is well recognized in the art and is intendedto include undesirable cell proliferation and/or aberrant cell growth,e.g., proliferation.

[0088] The term “modulate” includes effect(s) targeted tissue(s) thatprevent or inhibit growth of diseased tissue, which may ultimatelyaffect the physiological well being of the subject, e.g., in the contextof the therapeutic or prophylactic methods of the invention.

[0089] The term “solution” is intended to include those solutions, e.g.,aqueous solutions, which can be administered to a subject through adevice of the present invention without subsequent adverse effects. Inparticular, the solution should not diminish the strength, quality, orwavelength of energy emitted, e.g., laser energy, from the opticalapparatus. In general, the solution is considered a pharmaceuticallyacceptable carrier or vehicle.

[0090] Each solution must be “acceptable” in the sense of not beinginjurious to the patient. Some examples of materials which can serve asacceptable carriers include excipients, such as cocoa butter andsuppository waxes; oils, such as peanut oil, cottonseed oil, saffloweroil, sesame oil, olive oil, corn oil and soybean oil; glycols, such aspropylene glycol; polyols, such as glycerin, sorbitol, mannitol andpolyethylene glycol; esters, such as ethyl oleate and ethyl laurate;agar; buffering agents, such as magnesium hydroxide and aluminumhydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer'ssolution; ethyl alcohol; phosphate buffer solutions; and other non-toxiccompatible substances employed in pharmaceutical formulations.

[0091] The solution can also include adjuvants such as wetting agents,emulsifying and suspending agents, lubricants, such as sodium laurylsulfate and magnesium stearate, as well as coloring agents, releaseagents, coating agents, preservative agents and antioxidants can also bepresent in the solutions.

[0092] Examples of pharmaceutically acceptable antioxidants useful inthe solutions include: water soluble antioxidants, such as ascorbicacid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite,sodium sulfite and the like; oil-soluble antioxidants, such as ascorbylpalmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene(BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; andmetal chelating agents, such as citric acid, ethylenediamine tetraaceticacid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.

[0093] Solutions useful in the methods of the invention includeemulsions, microemulsions, solutions, suspensions, syrups and elixirs.The solution may contain inert diluents commonly used in the art, suchas, for example, water or other solvents, solubilizing agents andemulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate,ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol,1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn,germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol,polyethylene glycols and fatty acid esters of sorbitan, and mixturesthereof.

[0094] The term “modify” is intended to encompass those changes thetargeted tissue site, e.g., the surface, that cause the tissue to nolonger have undesired properties. For example, treatment of the anteriorwall of the right atrium by the present invention changes the path ofelectrical conduction after photonic treatment. The result is aconduction block which redirects conduction through the tissue andprevents the conduction from traveling across the atrial wall as it didprior to treatment.

[0095] The present invention also pertains to methods for forming anannular lesion in a tissue by ablation, coagulation and/orphototherapeutic processes. The methods introduce an optical apparatusproximate to a tissue site via, for example, a catheter. The opticalapparatus includes a modified optical wave guide that is incommunication with a light transmitting optical fiber. Energy istransmitted through the optical fiber, such that radiation propagatingthrough the optical fiber and wave guide projects an annular lightpattern, e.g., a circle, ring, halo or an outline or a shape formed byand projected from the modified wave guide. Preferably, the light isprojected through a graded intensity lens that is adjacent to theoptical wave guide. This additional step attenuates aberrations in thelight pattern and facilitates the forward annular projection of thetherapeutic light. By these methods, an annular lesion can be formed intissue. In certain embodiments, the tissue forms a lumen, e.g.,vascular, atrial, brachial, uretral, etc.

[0096] The present invention further pertains to methods for formingannular lesions in cardiac tissue, e.g., trabecular tissue, by ablation,coagulation and/or phototherapeutic processes. The methods includeintroduction of an optical apparatus proximate to cardiac tissue via,for example, a catheter. The optical apparatus includes an optical waveguide in communication with a light transmitting optical fiber andpreferably, a GRIN lens. Energy is transmitted through the opticalfiber, such that radiation propagated through the optical fiber, waveguide and GRIN lens is forwardly projects an annular light pattern,e.g., a circle or a halo. By these methods, an annular lesion can beformed in cardiac tissue.

[0097] The term “trabecular” is well recognized in the art and isintended to include tissue, e.g., cardiac tissue, which is a elastictissue often formed of bands and cords called trabeculae consisting offibrous tissue, elastic fibers and muscle fibers.

[0098] The present invention also pertains to methods method fortreating or preventing atrial arrhythmias by ablation, coagulation orphotochemical processes. The methods include introducing an opticalapparatus proximate to atrial tissue via, for example, a catheter. Theoptical apparatus includes an optical wave guide in communication with alight transmitting optical fiber. Energy is transmitted through theoptical fiber, such that radiation propagating through the optical fiberand wave guide projects an annular light pattern. The annular lightpattern forms an annular lesion in the atrial tissue, thereby treatingor preventing atrial fibrillation. The methods of the invention can beperformed therapeutically or prophylactically.

[0099] Atrial fibrillation and atrial flutter are abnormalities in therhythm or rate of the heart beat. For an adult at rest, the heartnormally beats between 60 and 80 beats per minute, but when atrialfibrillation occurs, the atria may beat irregularly and very rapidlybetween 350 and 600 times per minute. This causes the ventricles to beatirregularly in response as they try to keep up with the atria. Atrialflutter is similar to atrial fibrillation. The atrial contractions areless rapid, however, usually between 200 to 400 beats per minute, andare regular. Atrial flutter is often associated with a heart attack ormay occur after heart or lung surgery. Atrial fibrillation often resultsfrom a myriad of heart conditions such as angina, tachycardia, heartattack, heart valve problems, and even high blood pressure. All of theseconditions can cause stretching and scarring of the atria that interferewith the heart conduction system. The heart muscle can be weakened ifepisodes lasting several months or longer (with rapid heart rates)occur. Briefer episodes only cause problems if the heart rate is veryfast or if the patient has a serious heart problem in addition to theatrial fibrillation.

[0100] In FIGS. 9 and 10, apparatus 30, constructed in accordance withthe present invention, is depicted in its unexpanded and expanded formwithin a body cavity such as a lumen of a blood vessel 34. Flexibleelongate member 32 includes at least one lumen 36 extending the lengththereof from a proximal end to a distal end and can include, optionally,cap 48. Openings 38 in the side wall of the 32 define one or more poresthat provide fluid communication between the lumen 40 and an outerballoon 42, which can be bonded at proximal end 44 and distal end 46 toflexible elongate member 32. Optical apparatus 10 can be slidablypositioned within lumen 36 adjacent to balloon 42. Apparatus 30 canfurther include reflectance fiber 76 to monitor the progress oftreatment as described infra. Optical apparatus 10 includes opticalfiber 12, modified wave guide 14 and GRIN lens 26. As shown in FIG. 10,injection of fluid or gas, through lumen 40 and pores 38, forces thefluid or gas to flow out of the pores 38 to fill the chamber 50 withinthe balloon 42, thereby inflating balloon 42. In a preferred embodiment,the balloon is spherical or tear drop shaped. Preferably, flexibleelongate member 32 and balloon 42 are energy transparent.

[0101] By injecting a suitable solution or gas into chamber 50, balloon42 can be inflated to engage body tissue (e.g., the interior surface ofa blood vessel or other body lumen or tissue surrounding a natural orexcised interstitial space within the body). In one embodiment, balloon42 is non-porous and can engage the body tissue over a substantialportion of its length, thereby eliminating blood and/or other bodyfluids.

[0102] In FIG. 11, apparatus 30, constructed in accordance with thepresent invention, is depicted in its deflated position. Balloon 42resides within lumen 36 of flexible elongate member 32 and is fixedlyattached at distal end 52. Apparatus 30 can further include reflectancefiber 76 to monitor the progress of treatment as described infra. As asolution or gas is injected through lumen 36, balloon 42 expandsoutwardly from flexible elongate member 32 as shown in FIG. 12. Opticalapparatus 10 can be slidably positioned within lumen 36 within balloon42. Optical apparatus 10 includes optical fiber 12, modified wave guide14 and GRIN lens 26. The expansion of balloon 42 is dependent upon thelength of balloon 42, the type of balloon material and the appliedpressure of solution or gas. By this method, balloon 42 can conform tothe body cavity to which it is proximate. In a preferred embodiment,balloon 42 is non-porous. Preferably, flexible elongate member 32 andballoon 42 are energy transparent.

[0103] A preferred embodiment is depicted in FIGS. 13 and 13A having asilicone balloon anchor 54 (not inflated). Optical apparatus 10 can beslidably positioned within lumen 36 adjacent to balloon 42. Opticalapparatus 10 includes optical fiber 12, modified wave guide 14 and GRINlens 26. Gas, e.g., air, or a liquid can be injected into lumen 36(shown partially in phantom) to inflate silicone balloon anchor 54 ifrequired. A solution, e.g., water, saline, is injected through lumen 40to inflate balloon 42. Apparatus 30 can further include reflectancefiber 76 to monitor the progress of treatment as described infra. In oneembodiment, balloon 42 is preshaped to form a parabolic like shape. Thisis accomplished by shaping and melting a TEFLON® film in a preshapedmold to effect the desired form. The difference in refractive indexbetween the gas or liquid within lumen 36 and the liquid in chamber 50facilitates the projection of annular light beam 56 to be emitted at aradical angle from either wave guide 14 through GRIN lens 26.

[0104] The devices described in FIGS. 1-13 can be used for treating,e.g., ablating, coagulating and/or phototherapeutically treatingendocardial surfaces which promote arrhythmias or other disease statesor conditions. For example, atrial therapies can be performed byinserting an apparatus of the invention 30 into the femoral vein.Flexible elongate member 32 having balloon 42 fixedly attached is guidedthrough the inferior vena cava, and into the right atrium, and ifrequired, it is guided into the left atrium via atrial septal puncture.Left ventricular treatment can be performed by inserting flexibleelongate member 32 into the femoral artery. Flexible elongate member 32is guided through the iliac artery, the aorta, through the aortic valveand into the left ventricle. Once balloon 42 is proximate to the tissueablation site, a solution can be injected through lumen 36 or 40 toforce blood and/or body fluids away from the treatment site. Opticalapparatus 10 is guided through flexible member 32 via lumen 36 to aposition proximate to the tissue ablation site and energy, e.g., laserenergy, is emitted through balloon 42. Preferably, the composition offlexible elongate member 32 and balloon 42 are transparent to the energyemitted through optical apparatus 10.

[0105]FIG. 14 depicts annular lesions 55 formed on the inside ofpulmonary veins by the above described methods. It is consideredadvantageous to form the annular lesions 55 on the atrial surface/veininterface, thereby preventing propagation of aberrant electrical wavesthrough the cardiac region. Preferably, the lesion(s) completelyencircles the inner lumen of the vein(s).

[0106] In the present invention, reflective feedback is used to monitorthe state of coagulation, ablation and/or phototherapeutic processes ofthe treatment site so as to allow an optimal dose by either manipulationof the energy level or exposure time, or by controlling the sweep ofenergy across an exposure path.

[0107] Reflectance changes can also be employed by a control means inthe present invention to adjust or terminate laser operation.

[0108] In another aspect of the invention, a real-time display means canbe incorporated into a surgical microscope or goggles worn by aclinician during the procedure to provide a visual display of the stateof tissue coagulation simultaneously with the viewing of the surgicalsite. The display can reveal reflectance values at one or more specificwavelengths (preferably, chosen for their sensitivity to the onset andoptimal state of tissue modification), as well as display a warning ofthe onset of tissue carbonization.

[0109] In one method, according to the invention, application of laserto a biological structure(s ) while the reflectance of light from theirradiated site is monitored. Changes in scattering due to coagulation,ablation, phototherapeutic effects or crosslinking of the tissue willcause a reflectance change. In addition, dehydration due to laserexposure also affects the site's reflection. The reflectance can bemonitored in real-time to determine the optimal exposure duration or aidas visual feedback in the timing used in sweeping the energy across thetreatment site during the procedure.

[0110] In FIG. 15, a schematic block diagram of a laser tissue treatmentsystem 56 is shown, including a laser 58, power supply 60, controller 62and reflectance monitor 64. The system further includes opticalapparatus 30, and, optionally, illumination source 66, display 68 and/ortuner 70. In use, the output of laser 58 is delivered, preferably viaoptical apparatus 30, to treatment site 72 to phototherapeutically treatselected tissue. As the laser beam irradiates treatment site 72 thebiological tissue of the site is coagulated, ablated and/orphototherapeutically treated. The degree of treatment is determined bythe reflectance monitor 64, which provides electrical signals tocontroller 62 in order to control the procedure. The reflectance monitor64 receives light reflected by the site from a broadband or white lightillumination source 66 via fiber 67 and/or from laser 58 via opticalapparatus 30. In addition to controlling the laser operationautomatically, the reflectance monitor 64 and/or controller 62 can alsoprovide signals to a display 68 to provide visual and/or audio feedbackto the clinical user. Optional tuner 70 can also be employed by the user(or automatically controlled by controller 62) to adjust the wavelengthof the annealing radiation beam.

[0111]FIG. 16 is a more detailed schematic diagram of a reflectancemonitor 64, including a coupling port 74 for coupling with one or morefibers 76 to receive reflectance signals. A preferred reflectance fiberis a 100 micron diameter silica pyrocoat fiber from Spectran (Spectran,Conn., part number CF04406-11). The reflectance monitor 64 can furtherinclude a focusing lens 78 and first and second beam splitting elements80 and 82, which serve to divide the reflected light into 3 (or more)different beams for processing. As shown in FIG. 16, a first beam istransmitted to a first optical filter 84 to detector 86 (providing, forexample, measurement of reflected light at wavelengths shorter than 0.7micrometers). A second portion of the reflected light signal istransmitted by beam splitter 82 through a second optical filter 88 todetector 90 (e.g., providing measurement of light at wavelengths shorterthan 1.1 micrometers). Finally, a third portion of the reflected lightis transmitted to photodetector 92 (e.g., for measurement of reflectedlight at wavelengths greater than 1.6 micrometers). Each of the detectorelements 86, 90 and 92 generate electrical signals in response to theintensity of light at particular wavelengths.

[0112] The detector elements 86, 90 and 92 preferably includesynchronous demodulation circuitry and are used in conjunction with amodulated illumination source to suppress any artifacts caused by straylight or the ambient environment. (It should be apparent that otheroptical arrangements can be employed to obtain multiple wavelengthanalysis, including the use, for example, of dichroic elements, eitheras beam splitters or in conjunction with such beam splitters, toeffectively pass particular wavelengths to specific detector elements.It should also be apparent that more than three discreet wavelengths canbe measured, depending upon the particular application.) The signalsfrom the detector elements can then be transmitted to a controllerand/or a display element (as shown in FIG. 15).

[0113] In the controller, signals from the reflectance monitor areanalyzed to determine the degree of coagulation, ablation and/orphototherapeutic effect(s) which is occurring in the biological tissueexposed to the laser radiation. Typically, such treatment is performedfor 100 seconds or less. Such analysis can generate control signalswhich will progressively reduce the laser output energy over time as aparticular site experiences cumulative exposure. The control signals canfurther provide for an automatic shut-off of the laser when the optimalstate of treatment has been exceeded and/or the onset of carbonizationis occurring.

[0114] In use, the apparatus of the present invention can be employed toanalyze the degree of treatment by comparing the reflectance ratios of asite at two or more wavelengths. Preferably, intensity readings forthree or more wavelength ranges are employed in order to accuratelyassess the degree of treatment and to ensure that the optimal state isnot exceeded. The particular wavelengths to be monitored will, ofcourse, vary with the particular tissue undergoing treatment. Althoughthe tissue type (e.g., blood-containing tissue or that which isrelatively blood-free) will vary, the general principles of theinvention, as disclosed herein, can be readily applied by those skilledin the art to diverse procedures in which the phototherapeutic treatmentof biological materials is desired.

[0115] Those skilled in the art will know, or be able to ascertain,using no more than routine experimentation, many equivalents to thespecific embodiments of the invention described herein. These and allother equivalents are intended to be encompassed by the followingclaims. All publications and references cited herein including those inthe background section are expressly incorporated herein by reference intheir entirety.

What is claimed is:
 1. A phototherapeutic apparatus comprising a lighttransmitting optical fiber and an optical wave guide for projecting anannular pattern of light onto target tissue, such that radiationpropagating through said optical fiber when connected to said wave guideprojects an annular pattern of phototherapeutic radiation.
 2. Theapparatus of claim 1, wherein said optical wave guide comprises a quartzelement.
 3. The apparatus of claim 1, wherein said optical wave guidecomprises an acrylic element.
 4. The apparatus of claim 1, wherein saidfiber is capable of transmitting radiation in at least one range ofwavelengths between about 200 nanometers and about 2400 nanometers. 5.The apparatus of claim 4, wherein said fiber is capable of transmittingradiation at a wavelength of about 915 nanometers.
 6. The apparatus ofclaim 1, wherein said fiber is capable of transmitting ultravioletradiation.
 7. The apparatus of claim 6, wherein said fiber is capable oftransmitting ultraviolet light in at least one range of wavelengthsbetween about 200 nanometers and about 400 nanometers.
 8. The apparatusof claim 1, wherein said apparatus further comprises a graded index lensadjacent to said optical wave guide for projecting said light pattern.9. The apparatus of claim 1, wherein said apparatus further comprises arefractive lens adjacent to said optical wave guide for projecting saidlight pattern.
 10. A method for forming an annular lesion in a tissue byphototherapy, comprising the steps of: introducing an optical apparatusproximate to a tissue site, said optical apparatus having an opticalwave guide in communication with a light transmitting optical fiber; andtransmitting energy through said optical fiber, such that radiationpropagating through said optical fiber when connected to said wave guideprojects an annular light pattern, whereby an annular lesion is formedin said tissue.
 11. The method of claim 10, wherein said radiation iscoherent light.
 12. The method of claim 11, wherein said coherent lighthas a wavelength between about 200 nanometers and about 2400 nanometers.13. The method of claim 12, wherein said coherent light has a wavelengthof about 915 nanometers.
 14. The method of claim 11, wherein saidradiation is ultraviolet light.
 15. The method of claim 14, wherein saidultraviolet light has a wavelength between about 200 nanometers andabout 400 nanometers.
 16. The method of claim 10, further including thestep of passing said annular light pattern through a graded index lensadjacent to said optical wave guide for projecting said light pattern.17. A method for forming an annular lesion on endocardial tissue byphototherapeutic processes, comprising the steps of: introducing anoptical apparatus proximate to endocardial tissue, said opticalapparatus having an optical wave guide in communication with a lighttransmitting optical fiber; and transmitting energy through said opticalfiber, such that radiation propagating through said optical fiber whenconnected to said wave guide projects an annular light pattern, wherebyan annular lesion is formed in said endocardial tissue.
 18. A method fortreating or preventing atrial arrhythmias by phototherapy, comprisingthe steps of: introducing an optical apparatus proximate to atrialtissue, said optical apparatus having an optical wave guide incommunication with a light transmitting optical fiber; and transmittingenergy through said optical fiber, such that radiation propagatingthrough said optical fiber when connected to said wave guide projects anannular light pattern, whereby an annular lesion is formed in saidatrial tissue, thereby treating or preventing atrial arrhythmias.
 19. Aphototherapeutic apparatus comprising a laser for delivering laserenergy to a target tissue; a light transmitting optical fiber and anoptical wave guide for projecting an annular pattern of light onto saidtarget tissue, said optical fiber and optical wave guide incommunication with said laser such that radiation propagating throughsaid optical fiber when connected to said wave guide projects an annularpattern of phototherapeutic radiation; a reflectance sensor formeasuring intensity of light reflected from said tissue whileilluminating said tissue; a monitor connected to said reflectance sensorfor monitoring changes in the intensity of light reflected from saidtissue; an analyzer connected to said monitor for determining the degreeof therapeutic treatment based upon said monitored changes in saidtissue; and a controller connected to said analyzer and laser forcontrolling the output of said laser in response to said reflected lightfrom said treated tissue.
 20. A method for treating or preventing atrialarrhythmias by phototherapy, comprising the steps of: introducing anoptical apparatus proximate to atrial tissue, said optical apparatushaving an optical wave guide in communication with a light transmittingoptical fiber; transmitting laser energy through said optical fiber,such that radiation propagating through said optical fiber whenconnected to said wave guide projects an annular light pattern;measuring the intensity of light reflected from said target tissue; andcontrolling the energy applied to said site in response to monitoredchanges in the intensity of said light reflected from said targettissue, thereby treating or preventing atrial arrhythmias.